PROJECT SUMMARY The goal of this project is to map transitions in brain and behavior over the first 6 months of life in infants at high- and low-risk for Autism Spectrum Disorders (ASD). This study builds on results demonstrating that a basic mechanism of social adaptive action?looking at the eyes of others?was already in decline in the first 6 months of life of infants with ASD (Jones & Klin, Nature, 2013). Interestingly, these findings contradicted prior hypotheses postulating an absence of social adaptive orientation in ASD from birth: early levels of eye-looking were not immediately diminished in infants later diagnosed with ASD; instead, these infants exhibited a slight but statistically significant increase in eye-looking at 2 months, which then declined. Together with evidence of early normative transitions from experience-expectant mechanisms (that is, largely subcortically-mediated ?reflex-like? predispositions) to experience-dependent ones (that is, largely cortically-mediated adaptive actions that build upon early newborn experiences), these data suggest a very specific hypothesis in ASD: reflex-like predispositions may be initially present, whilst early pivotal transitions, dependent upon the way in which initial predispositions are integrated into contingent social interaction, are disrupted. The proposed study will directly test this hypothesis. Aim 1 will identify brain networks associated with transitions from reflex-like/experience- expectant to interactive/experience-dependent forms of social adaptive action, and will identify the developmental phase?experience-expectant or experience-dependent?in which disruptions in brain and behavior first emerge in ASD. Aims 2 and 3 will identify aspects of brain maturation and early infant experience that are necessary and/or sufficient for guiding brain-behavior transitions over the first 6 months of life. Aim 2 will identify aspects of brain maturation that drive the emergence of sensitivity to social contingency, a critical mechanism of social interaction between infant and caregiver. Aim 3 will identify aspects of early infant experience that are necessary and/or sufficient for shaping the development of infant social brain networks. Brain-behavior transitions will be measured in the same cohort of infants shared by Projects I-IV. Measures (in brain and behavior) are harmonized with Project V to facilitate comparisons between human and model systems. Anatomical, structural, and functional MRI scans will be collected at 3 time points between birth and 6 months, and region-of-interest and network analyses will be used to characterize how subcortical and cortical networks interact and reorganize over infants? first 6 months. Bidirectional relationships between developmental change in the brain and developmental change in behavior (measured in Projects I and II) will be examined using innovative statistical approaches for modeling time-varying longitudinal data and for detecting statistical causality within complex systems. By intensively studying the brain-behavior bases of emerging social disability in very early infancy, this research will offer new mechanistic insight into the pathogenesis of ASD, and identify new targets for innovative early interventions.